Comparing biomarkers for COVID-19 disease with commonly associated preexisting conditions and complications

Abstract

Severe coronavirus disease 2019 (COVID-19) has been associated with certain preexisting health conditions and can cause respiratory failure along with other multi-organ injuries. However, the mechanism of these relationships is unclear, and prognostic biomarkers for the disease and its systemic complications are lacking. This study aims to examine the plasma protein profile of COVID-19 patients and evaluate overlapping protein modules with biomarkers of common comorbidities. Blood samples were collected from COVID-19 cases (n=307) and negative controls (n=78) among patients with acute respiratory distress. Proteins were measured by proximity extension assay utilizing next-generation sequencing technology. Its associations to COVID-19 disease characteristics were compared to that of preexisting conditions and established biomarkers for myocardial infarction (MI), stroke, hypertension, diabetes, smoking, and chronic kidney disease. Several proteins were differentially expressed in COVID-19, including multiple pro-inflammatory cytokines such as IFN-gamma, CXCL10, and CCL7/MCP-3. Elevated IL-6 was associated with increased severity, while baseline IL1RL1/ST2 levels were associated with a worse prognosis. Network analysis identified several protein modules associated with COVID-19 disease characteristics overlapping with processes of preexisting hypertension and impaired kidney function. BNP and NTpro-BNP, markers for MI and stroke, increased with disease progression and were positively associated with severity. MMP12 was similarly elevated and has been previously linked to smoking and inflammation in emphysema, along with increased cardiovascular disease risk. In conclusion, this study provides an overview of the systemic effects of COVID-19 and candidate biomarkers for clinical assessment of disease progression and the risk of systemic complications.

Longitudinal proteomic profiling of dialysis patients with COVID-19 reveals markers of severity and predictors of death

“…In agreement with previous studies [10,27], CXCL10, a chemokine secreted in response to IFN-gamma, was elevated in COVID-19 patients and correlated with severity. DDX58 and IL6 were also among the most strongly upregulated proteins in COVID-19 positive patients and correlated with disease severity, demonstrating the presence of similar immune responses to the ones seen in non-ESKD COVID-19 patients [27]. Of note, the neutrophil proteases PRTN3 and MPO ( Fig.…”

“…Consistent with the latter, flow cytometric analyses in COVID-19 have shown evidence of phenotypic changes in the circulating monocytes such as expression of cell proliferation markers that occurs when there is premature release of monocytes from the marrow due to an emergency myelopoesis [26]. In agreement with previous studies [10,27], CXCL10, a chemokine secreted in response to IFN-gamma, was elevated in COVID-19 patients and correlated with severity. DDX58 and IL6 were also among the most strongly upregulated proteins in COVID-19 positive patients and correlated with disease severity, demonstrating the presence of similar immune responses to the ones seen in non-ESKD COVID-19 patients [27].…”

“…Other groups have studied the plasma or serum proteome in COVID-19 [8–10] using either mass spectrometry or immunoassays including the Olink platform. We observed greater similarities with other studies that used immunoassays [9,10,27], including the associations between severity and leucocyte chemokines ( Supplementary Tables 4,6 ). However, we observed very little overlap with the mass spectrometry study of Shen et al [8].…”

“…Complement C5 inhibition is under investigation in the treatment of severe COVID-19 infection [33,40] and our findings support this approach. An intriguing association is the prominence of KRT19 in our analyses and a pre-print [27] ( Supplementary Table 4,6 ). KRT19 is an intermediate filament protein, important for the structural integrity of epithelial cells [41].…”

Early measurement of blood sST2 is a good predictor of death and poor outcomes in patients admitted for COVID-19 infection

“…Baseline sST2 levels were associated with baseline disease severity and with worse outcomes (death or requiring ventilation in 28 days follow-up). sST2 values peaked at day 3 16 . Because the IL-33/ST2 axis is involved in immune response to viral infections, Zeng et al .…”